“First-pass” metabolism of paracetamol in rat liver

Paracetamol was administered intraperitoneally or intravenously to male rats. Its ‘availability’ in the systemic circulation after intraperitoneal administration was only 34% of that after intravenous administration. This suggested a high “first-pass” metabolism of intraperitoneally administered drug, which was confirmed using the rat isolated perfused liver. The hepatic extraction ratio for paracetamol decreased with increasing concentrations of the drug in the perfusion fluid, suggesting that gastric emptying rate, by controlling the concentration of drug in the portal vein, could influence the amount of “first-pass” metabolism.